Current longevity protocol: Should I add rapamycin?

This is my first post here, and I’m hoping to get some insights from people with similar protocols. In particular, I’m curious to hear people’s perspective on rapamycin given my current regimen.

I’m a 44-year old male living in Toronto (hello to my fellow Canadians).

I’ve been implementing anti-aging practices for decades now.

My current protocol is the following:

  • Vegetarian diet, mostly plant-based, occasional eggs and cheese
  • 16/8 intermittent fast 5+ days a week
  • Progressive resistance training 6 days a week
  • Moderate cardiovascular exercise daily and intense training 1 day a week
  • 1,700 mg of metformin daily, divided in two doses
  • 300 mg nicotinamide riboside daily
  • Senolytics (Life Extension Senolytic Activator) weekly
  • Other interventions: Omega-3s, curcumin, coenzyme Q10, Life Extension Ultra Prostate, Life Extension Mitochondrial Energy Optimizer, Life Extension Mix Tablets)

I had recent bloodwork, ultrasound, and body composition analysis, and (knock on wood) all is well. I did have low ferritin, but I think this is related to reducing consumption of fortified grain products because my kids have celiac and we had to change what we eat at home. So I’m taking a low dose iron supplement for a few months to correct the issue.

I’m now considering rapamycin, and wondering if anyone out there with a similar protocol has experience taking it and, if so, what your dose, dosing regimen, and results (including side effects) have been.

Thanks!

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  • Forgot to also include l-theanine, ashwagandha, and melatonin as other current interventions.

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    • Simon Smith I'm not yet into self-experimentation with Rapamycin, so I'm still far less competent than others. The evolution of the personal experiments here visible progresses quickly. Looking at other people practicing CR so far, at this intermediate stage of the evolution of Age Reversal (notably Bill Faloon and David Sinclair): if your body takes well Calorie Restriction, then you might not need Rapamycin. Steve Horvat's recent description of Biogenetic clocks at the EARD conference shows that Rapamycin stops the clock- and i think Drs. Green and Blagosklonny are trying to see if, used a bit differently, it could rejuvinate. It's very useful for people who would have trouble fasting (I had wheatgrass fasts in the past, but at 71 my muscle is reduced, my metabolism still requires food, so I was prescribed Rapamycin, Dasatinib and told to read dr. Vlassara's team's studies or her "The A.G.E. Less Diet" book (which is not a diet, just easy avoiding of Advanced Glycation Endproducts food - it does not seem to be given much importance, it's adaptable to all diets, I personally guess it can't hurt).
      As for Senolytics, they've been found powerful; I'm not sure how the Life Extension one compares. I used to take it with many of the other LEF supplements you take - I took even more, but I have no idea how much they helped. I understand there are two types of senescent cells, one should be somewhat spared - I don't remember the source..
      I find there are so many valuable people, including many doctors, on this forum, the Age Reversal Network has its own doctors, is conducting valuable experiments, one could possibly take part in them. On Rapamycin the PEARL study seems to be under way, (Lifespan.io). Other rejuvination factors have complexities for them to work (NAD is one of these, like Eric Verdin has just explained at EARD). There can be also interactions that can make one therapy contrast the others; I understand it comes down to careful timing, so I'd say that should not stop one from using more than one approach as long as one understands the timing - references on the forum and in specialised research studies (like the many found on Fight Aging). Some try to put the puzzle together, some self- experimenters try to get the maximum benefit from as many approaches as they can understand or be well advised on.
      I must concentrate, like many I might have to check back here less often for a while. It's good to keep up with the latest info, then one has to bring it into one's use and balance life also. All the best! Flavio

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    • Flavio Ferlitz thanks! 

      I practiced caloric restriction for several years but found myself losing too much muscle mass. This actually accelerated when I began doing progressive resistance training more aggressively, and so I switched to 16/8 time-restricted eating. Since then I've gained strength and muscle mass, though admittedly also a bit of fat mass.

      I'm very interested in the results of the PEARL study, but they're explicitly excluding people from taking metformin during the trial, so I won't get an answer on the combination there. 

      Data from the Interventions Testing Program suggests that rapamycin plus metformin is at least as effective as rapamycin alone. Metformin may also counteract rapamycin's potentially negative (though not necessarily—I've read that this is benign, equivalent to the impact of fasting) impact on blood glucose (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892694/).

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      • SD
      • MAC2
      • 1 mth ago
      • Reported - view

      Simon Smith Hi Simon from a fellow Torontonian. 56 yo male. Fired by family doctor, took on a functional medicine doctor (FMD), focused on prevention like most people here. Went strict keto (PLANT FATS BASED), one meal a day 5 years ago (for the powerful signalling metabolites in ketones, especially neurocognitive). I was intrigued by your comment re CR and muscle mass loss. I started daily resistance (30 mins free weights) followed by 5km treadmill (130 bpm) exercise regiment simultaneously (yes exercise is clearly my #1 health intervention). I promptly lost 50 lbs on the strict keto regiment over about 6-12 months. My muscle mass, however, has exploded on my regiment, and has nothing to do with diet or protein intake (I consume max 50 g net protein/day to stay keto)...but RESISTANCE training. Amino acids don't potentiate muscle hypertrophy...resistance exercise does. My weight has been very stable the last few years. I am in a tweaking mode...trading off eliminating the last vestiges of fat weight loss via very slight calorie reduction whilst increasing muscle mass with higher resistance exercise; increasing lean muscle build with fat loss to maintain weight. I take a large stack of supplements, several you referenced and more.

      I did add Rapamycin to my stack in January of this year. Started at 4mg/week, now at 6mg/week, will keep increasing/testing biomarkers. Haven't had any side effects, glucose or lipid dysregulation. Have noticed IMPROVED liver and kidney biomarkers (eGFR is 100, like a 20 yr old), and reduced liver GGT, and very low uric acid.

      Re Ferritin, I am of the "dumping as much iron as possible" camp. It's pro oxidative and PRO-AGING (several papers now making this association). I donate 450ml every 7 weeks (https://www.blood.ca/en), so I am completely turning over my whole body blood supply (including plasma) approx every 18 months, which is rejuvenating as it's own intervention. I had my Ferritin down to 12 last test (2 weeks after a donation). It normally ranges between 20-35 between donations. NO anemia like symptoms. Ferritin is NOT a good cellular biomarker for iron stores, . They tell you not to exercise for 24 hrs...I'm on the treadmill same day!

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    • SD thanks for this.

      I was doing caloric restriction, then added metformin, and then added progressive resistance training, switching from a body weight-only workout. I was losing weight and muscle mass, though gaining strength. I switched to time-restricted eating with unlimited (mostly plant-based) calories, and added a lot of muscle mass. My resistance training routine didn't change (I use Fitbod—awesome app), and I kept taking metformin. The earlier muscle loss may be related to metformin's blunting of hypertrophy (https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13039).

      I assume you're not currently taking metformin with rapamycin? Just the rapamycin?

      I'd also be curious to hear other people's perspective on ferritin. I hear you about iron. Just wondering if there's an optimal zone and if anyone has data to back it.

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      • SD
      • MAC2
      • 1 mth ago
      • Reported - view

      Simon Smith yes aware of the literature on metformin/exercise blunting. I don’t take metformin. With my ketogenic area under the curve, I am already blunting AMPK, and Rapamycin blows away metformin in terms of extending longevity in every animal model it’s been studied. Once I understood that I could continue my exercise regiment on Rapamycin, that’s when I dove in. Dump all the iron you can’t until you hit anemia. There’s a big pool there, depending on your unique N=1 profile. 

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    • SD will do some research on ferritin. I wonder if there's any population data out there on mortality risk of different levels.

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      • SD
      • MAC2
      • 1 mth ago
      • Reported - view

      Simon Smith Do you know your genetic iron genes? For example, from a 23andme test?

      > https://www.xcode.life/23andme-raw-data/hereditary-hemochromatosis-get-your-hfe-status-using-dna-raw-data/

      > https://www.geneticlifehacks.com/building-up-iron-genetics-diet-and-health-effects/

      I am homozygous H63D, means I tend to have higher Ferritin. In fact, my very first ferritin test several years ago, it came back at 350 (never donated blood, I was 51 yo).

      https://irondisorders.org/wp-content/uploads/2019/12/Genetic-H63D-2020.pdf

      Next lab bloodwork, do a full iron panel, and it's SATURATION that you want to look at, far more important than Ferritin.

      https://irondisorders.org/wp-content/uploads/2019/12/Iron-Avid-3-2020.pdf

      re Iron/Ferritin/Longevity;

      Total and Cause-Specific Mortality by Moderately and Markedly Increased Ferritin Concentrations: General Population Study and Meta-analysis

      > https://pubmed.ncbi.nlm.nih.gov/25156997/

      Multivariate genomic scan implicates novel loci and haem metabolism in human ageing

      > https://pubmed.ncbi.nlm.nih.gov/32678081/

      Blood donation and blood donor mortality after adjustment for a healthy donor effect

      > https://pubmed.ncbi.nlm.nih.gov/26098293/

      Iron as a target of chemoprevention for longevity in humans

      > https://pubmed.ncbi.nlm.nih.gov/21615276/

      The Risk of Too Much Iron: Normal Serum Ferritin Levels May Represent Significant Health Issues

      > https://isom.ca/wp-content/uploads/The-Risk-of-Too-Much-Iron-Normal-Serum-Ferritin-Levels-May-Represent-Significant-Health-Issues-28.4.pdf

      " It is hypothesized that optimum ferritin levels are at the low end of the normal reference range near the threshold for anaemia"

      Ferritin and Percent Transferrin Saturation Levels Predict Type 2 Diabetes Risk and Cardiovascular Disease Outcomes

          > https://pubmed.ncbi.nlm.nih.gov/28474556/

      Iron Accelerates Aging

         >  https://roguehealthandfitness.com/iron-accelerates-aging/

      Genetically predicted iron status and life expectancy

          > https://pubmed.ncbi.nlm.nih.gov/32690432/

      https://joshmitteldorf.scienceblog.com/2015/11/09/does-donating-blood-extend-your-life-expectancy/

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    • SD thanks! Going to use my Promethease account to look up that gene.

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      • SD
      • MAC2
      • 1 mth ago
      • Reported - view

      Simon Smith that’s not the only hemo gene, there are several others, and depending on what test and genome array that was available, it might only catch the main ones. 

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  • Watching this may help. It is long, but excellent.

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    • SCOTT WEANER thanks! I listened to Attia's interview with Kaeberlein the other day. He didn't talk explicitly about combining metformin with rapamycin, though, from what I recall.

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  • I do currently combine rapamycin with metformin. Do I know that any of it truly works? 

    Not really, but the research looks good for each drug.

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    • SCOTT WEANER great to hear! Would you mind sharing your dose and dosing regimen for each drug? And how long have you been using them together? (Also, any other details of your regimen that you're open to sharing.)

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      • Jim
      • Jim.1
      • 4 wk ago
      • Reported - view

      SCOTT WEANER  I am seventy years of age and also have begun to do both. Not certain if it works but at my age I have little to lose. High wine consumption probably dampens any benefits.

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  • I take rapamycin 6mg once weekly. The metformin is 750mg daily, with the plan to increase to 1,000mg.

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    • SCOTT WEANER appreciated. Last question (for now :)). Do you pulse the rapamycin, X weeks on and then X weeks off?

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  • I have not been pulsing it, just weekly. We are certainly flying by the seat of our pants!

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    • SCOTT WEANER thanks. Appreciated!

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  • Hello, 

    I am also 44, train strength or cardio almost every day, I take 500mg metformin before bed. I took 6 mg rapamycin every saterday combined with a 24h water fast for a week or 10. 10 days ago, I took 13 mg rapamycin followed with a 52h water fast with no adverse reactions. (my rapamycin is doctor prescribed).

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